阅读说明：本技术 抗病毒活性蔗渣木聚糖肉桂酸/间氯苯甲酸双酯的合成方法 (Synthesis method of antiviral active bagasse xylan cinnamic acid/m-chlorobenzoic acid diester ) 是由 李和平 杨锦武 李明坤 葛文旭 郑光绿 武晋雄 张淑芬 柴建啟 耿恺 杨莹莹 于 2019-10-22 设计创作，主要内容包括：本发明公开了一种抗病毒活性蔗渣木聚糖肉桂酸/间氯苯甲酸双酯的合成方法。以蔗渣木聚糖为主要原料,以肉桂酰氯为酯化剂,三乙胺为催化剂,首先在二氯甲烷溶剂中经酯化反应合成了蔗渣木聚糖肉桂酸酯；再以间氯苯甲酸钠盐溶液为酯化剂,732型强酸性阳离子交换树脂、<I>N,</I><I>N</I>’-二异丙基碳二亚胺为复合催化剂,经过二次酯化反应合成蔗渣木聚糖肉桂酸/间氯苯甲酸双酯。本发明通过两步酯化复合催化反应合成了产物蔗渣木聚糖肉桂酸/间氯苯甲酸双酯。由于肉桂酸和间氯苯甲酸两种活性基团的引入,不仅改善了原蔗渣木聚糖的理化性质,而且增强了蔗渣木聚糖衍生物的抗病毒活性。(The invention discloses a method for synthesizing antiviral active bagasse xylan cinnamic acid/m-chlorobenzoic acid diester. Bagasse xylan is used as a main raw material, cinnamoyl chloride is used as an esterifying agent, triethylamine is used as a catalyst, and bagasse xylan cinnamate is synthesized through an esterification reaction in a dichloromethane solvent; then using sodium meta-chlorobenzoate solution as esterifying agent, 732 type strong acid cation exchange resin, N, N ' -diisopropylcarbodiimide is used as a composite catalyst, and bagasse xylan cinnamic acid/m-chlorobenzoic acid diester is synthesized through a secondary esterification reaction. The invention synthesizes the product bagasse xylan cinnamic acid/m-chlorobenzoic acid diester through two-step esterification composite catalytic reaction. Due to the introduction of two active groups, namely cinnamic acid and m-chlorobenzoic acid, the physicochemical property of the original bagasse xylan is improved, and the antiviral activity of the bagasse xylan derivative is enhanced.)

1. A method for synthesizing antiviral active bagasse xylan cinnamic acid/m-chlorobenzoic acid diester is characterized by comprising the following specific steps:

(1) placing 15 ~ 20g of bagasse xylan into a vacuum constant-temperature drying oven at 60 ℃ for drying for 24 hours to obtain dry-based bagasse xylan;

(2) weighing 0.4 ~ 0.8.8 g cinnamoyl chloride into a 50mL beaker, adding 20 ~ 40mL analytical pure dichloromethane to obtain an esterifying agent solution, and pouring the esterifying agent solution into a 100mL constant-pressure dropping funnel for later use;

(3) weighing 3 ~ 6g of the dry-based bagasse xylan obtained in the step (1), placing the dry-based bagasse xylan into a 250mL four-neck flask provided with a stirrer, a thermometer and a reflux condensing device, sequentially adding 25 ~ 35mL of analytically pure dichloromethane and 1 ~ 2mL of analytically pure triethylamine, and stirring at room temperature for 30 ~ 50 minutes to obtain a bagasse xylan activation solution;

(4) heating the activated solution obtained in the step (3) to 60 ~ 70 ℃, then dropwise adding the esterifying agent solution obtained in the step (2) into a four-neck flask, controlling the dropwise adding time to be 20 ~ 40 minutes, continuously reacting for 2 ~ 3 hours after the dropwise adding of the esterifying agent solution is finished, and cooling the materials to room temperature;

(5) carrying out suction filtration on the material obtained in the step (4), sequentially washing and carrying out suction filtration by using 15 ~ 30mL of absolute ethyl alcohol, 30 ~ 40mL of analytically pure acetone and 20 ~ 30mL of deionized water respectively, and placing a filter cake in a constant-temperature vacuum drying oven at 50 ~ 60 ℃ for drying for 24 hours to obtain bagasse xylan cinnamate;

(6) sequentially adding 8 ~ 10g of m-chlorobenzoic acid and 30 ~ 40mL of 3% ~ 5% sodium hydroxide solution into a 250mL four-neck flask provided with a stirrer, a thermometer and a reflux condensing device, and stirring at room temperature for 20 ~ 40 minutes to obtain a p-chlorobenzoic acid sodium salt solution;

(7) weighing 8 ~ 10g of the bagasse xylan cinnamate obtained in the step (5), adding the bagasse xylan cinnamate into the sodium m-chlorobenzoate solution obtained in the step (6), stirring the solution at room temperature for 30 ~ 60 minutes, and adding 15 ~ 20mL of a solution containing 3% by mass and ~ 5% by massAdjusting pH of the reaction solution to 6 ~ 7 with hydrochloric acid, adding 0.2 ~ 0.3.3 g 732 type strongly acidic cation exchange resin and 1.5 ~ 2mL of analytically pureN, N' -diisopropylcarbodiimide, heating the system to 50 ~ 70 ℃, reacting for 3 ~ 5 hours under stirring, adjusting the pH of the system to 4 ~ 5 by using 10 ~ 20mL of hydrochloric acid solution with the mass fraction of 3% ~ 5% after the reaction is finished, cooling to room temperature, and continuing to stir for 40 ~ 60 minutes;

(8) pouring the material obtained in the step (7) into a 100mL beaker, adding 20 ~ 30mL of analytically pure absolute ethyl alcohol, precipitating for 30 ~ 40 minutes after uniformly stirring, filtering, washing with 10 ~ 15mL of deionized water and 10 ~ 15mL of analytically pure absolute ethyl alcohol respectively in sequence, performing suction filtration for 2 ~ 3 times, putting the filter cake into a watch glass, and drying in a vacuum constant-temperature drying oven at 50 ℃ for 24 hours to constant weight to obtain the product of bagasse xylan cinnamic acid/m-chlorobenzoic acid diester.

Technical Field

The invention relates to the field of fine chemical engineering, in particular to a method for synthesizing antiviral active bagasse xylan cinnamic acid/m-chlorobenzoic acid diester.

Background

AIDS (HIV), which poses a great threat to human health, is spread rapidly worldwide. In recent years, some research and research on xylan esterified derivatives have been conducted at home and abroad based on their biological activities in the anti-HIV field. The xylan has poor water solubility and low activity, and can make up the defects of the xylan through chemical modification such as esterification grafting, etherification and the like, and further improve the biological activity of the xylan. However, because only one bioactive group is introduced into the mono-esterification of xylan, the antiviral effect generated is not ideal, such as synthetic xylan sulfate, xylan phosphate, xylan carboxylate, and the like.

The xylan metachlorobenzoate has an antiviral effect, and in order to further improve the biological activity of the bagasse xylan, a second active group cinnamate is introduced to the bagasse xylan chains to carry out double esterification on the bagasse xylan to obtain the derivative, so that the biological activities of the bagasse xylan derivative such as the antiviral activity can be greatly improved.

The bagasse xylan is used as a main raw material, cinnamoyl chloride is used as an esterifying agent, triethylamine is used as a catalyst, and the bagasse xylan cinnamate is synthesized by esterification reaction in a dichloromethane solvent; and then synthesizing bagasse xylan cinnamic acid/m-chlorobenzoic acid diester through a secondary esterification reaction by using an m-chlorobenzoic acid sodium salt solution as an esterifying agent, 732 type strong acid cation exchange resin and N, N' -diisopropyl carbodiimide (DIC) as a composite catalyst.

Disclosure of Invention

The invention aims to enhance the antiviral activity of bagasse xylan, expand the application range of the bagasse xylan in the fields of medicines, foods and the like, and provide a synthetic method of antiviral activity bagasse xylan cinnamic acid/m-chlorobenzoic acid diester.

The method comprises the following specific steps:

(1) and (3) placing 15-20 g of bagasse xylan into a vacuum constant-temperature drying oven at 60 ℃ for drying for 24 hours to obtain the dry-based bagasse xylan.

(2) Weighing 0.4-0.8 g of cinnamoyl chloride into a 50mL beaker, adding 20-40 mL of analytically pure dichloromethane to obtain an esterifying agent solution, and pouring the esterifying agent solution into a 100mL constant-pressure dropping funnel for later use.

(3) Weighing 3-6 g of the dry-based bagasse xylan obtained in the step (1), placing the dry-based bagasse xylan into a 250mL four-neck flask provided with a stirrer, a thermometer and a reflux condensing device, sequentially adding 25-35 mL of analytically pure dichloromethane and 1-2 mL of analytically pure triethylamine, and stirring at room temperature for 30-50 minutes to obtain the bagasse xylan activating solution.

(4) And (3) heating the activated solution obtained in the step (3) to 60-70 ℃, and then dropwise adding the esterifying agent solution obtained in the step (2) into a four-neck flask, wherein the dropwise adding time is controlled to be 20-40 minutes. And after the esterification agent solution is dripped, continuously reacting for 2-3 hours, and cooling the material to room temperature.

(5) And (4) carrying out suction filtration on the material obtained in the step (4), and sequentially and respectively washing and carrying out suction filtration by using 15-30 mL of absolute ethyl alcohol, 30-40 mL of analytically pure acetone and 20-30 mL of deionized water. And (3) drying the filter cake in a constant-temperature vacuum drying oven at 50-60 ℃ for 24 hours to obtain the bagasse xylan cinnamate.

(6) Sequentially adding 8-10 g of m-chlorobenzoic acid and 30-40 mL of 3-5% sodium hydroxide solution by mass fraction into a 250mL four-neck flask provided with a stirrer, a thermometer and a reflux condensing device, and stirring at room temperature for 20-40 minutes to obtain a p-chlorobenzoic acid sodium salt solution.

(7) And (3) weighing 8-10 g of the bagasse xylan cinnamate obtained in the step (5), adding into the m-chlorobenzoic acid sodium salt solution obtained in the step (6), and stirring at room temperature for 30-60 minutes. Adding 15-20 mL of hydrochloric acid with the mass fraction of 3% -5% to adjust the pH of the reaction solution to 6-7, and then adding 0.2-0.3 g of 732 type strong acid cation exchange resin and 1.5-2 mL of analytically pure N, N' -diisopropylcarbodiimide; the temperature of the system is raised to 50-70 ℃, and the reaction is carried out for 3-5 hours under stirring. After the reaction is finished, adjusting the pH value of the system to 4-5 by using 10-20 mL of hydrochloric acid solution with the mass fraction of 3% -5%, cooling to room temperature, and continuously stirring for 40-60 minutes.

(8) And (3) pouring the material obtained in the step (7) into a 100mL beaker, adding 20-30 mL of analytically pure anhydrous ethanol, uniformly stirring, precipitating for 30-40 minutes, filtering, washing with 10-15 mL of deionized water and 10-15 mL of analytically pure anhydrous ethanol in sequence, and performing suction filtration for 2-3 times. And putting the filter cake into a watch glass, and conveying the filter cake into a vacuum constant-temperature drying oven at 50 ℃ for drying for 24 hours to constant weight to obtain the product of bagasse xylan cinnamic acid/m-chlorobenzoic acid diester.

(9) And (3) measuring the esterification substitution degree of the bagasse xylan cinnamic acid/m-chlorobenzoic acid diester obtained in the step (8) by adopting an acid-base titration method, wherein the specific operation method comprises the following steps: accurately weighing 0.5g of product sample, putting the product sample into a 50mL conical flask, adding 5mL of deionized water, fully shaking the mixture, dripping 2 drops of phenolphthalein reagent, titrating the mixture to light red by using a 0.1mol/L NaOH standard solution, and maintaining the red color within 30 seconds without removing the red color; then, continuously adding 2.5mL of 0.5mol/L NaOH standard solution, after shaking and saponifying for 2 hours at room temperature, titrating by using 0.5mol/L hydrochloric acid standard solution until the solution system is colorless, and recording the volume of HCl standard solution consumed by titration as V₁. Under the same conditions, blank titration is carried out by using bagasse xylan before esterification, and the volume V of consumed hydrochloric acid standard solution with the concentration of 0.5mol/L is recorded₀. Degree of Substitution (DS) of target product by esterification_c) The calculation formula of (a) is as follows:

in the formula:

W_c-bagasse woodThe polysaccharide cinnamic acid/m-chlorobenzoic acid diester contains ester carbonyl in percentage by mass;

V₀titrating the volume of the hydrochloric acid standard solution consumed by the bagasse xylan in unit mL;

V₁titrating the volume of the hydrochloric acid standard solution consumed by the target product sample in mL;

C_HCl-hydrochloric acid standard solution concentration, in mol/L;

m is the mass of the product sample in g;

DS_c-degree of substitution by esterification of bagasse xylan cinnamic acid/m-chlorobenzoic acid diester;

m and 132-acyl group of Carboxylic acid esterifying agent and relative molecular mass of the bagasse xylan anhydroxylose unit.

The invention synthesizes the product bagasse xylan cinnamic acid/m-chlorobenzoic acid diester through two-step esterification composite catalytic reaction. Due to the introduction of two active groups, namely cinnamic acid and m-chlorobenzoic acid, the physicochemical property of the original bagasse xylan is improved, and the antiviral activity of the bagasse xylan derivative is enhanced.

Drawings

FIG. 1 is an SEM photograph of raw bagasse xylan.

Figure 2 is an SEM photograph of bagasse xylan cinnamic acid/m-chlorobenzoic acid diester.

FIG. 3 is an IR chart of raw bagasse xylan.

Figure 4 is an IR diagram of bagasse xylan cinnamic acid/m-chlorobenzoic acid diester.

Figure 5 is an XRD pattern of raw bagasse xylan.

Figure 6 is an XRD pattern of bagasse xylan cinnamic acid/m-chlorobenzoic acid diester.

FIG. 7 shows TG and DTG curves of raw bagasse xylan.

FIG. 8 shows TG and DTG curves of bagasse xylan cinnamic acid/m-chlorobenzoic acid diester.

Detailed Description